LFTs.pdf

Microbiology

1. DCM & Surgery Msambweni
By Charles Ng’ang’a
Liver function tests

2. Liver function tests
•Liver function tests (LFTs or LFs) are
–groups of blood tests that give
–information about the state of a patient's liver.
–These tests include prothrombin
–time (PT/INR), aPTT, albumin, bilirubin
–(direct and indirect), and others.

3. General approach
•Cholestatic—intrahepatic/extrahepatic biliary obstruction
•Hepatocellular—hepatocyte damage (e.g. viral hepatitis,
drugs/toxins, ETOH, ischemia, malignant infiltration)
•Isolated hyperbilirubinemia—e.g. congestive hepatopathy
Pt with hxof intermittent abdominal pain associated with meals
undergoes RUQ (Right upper Quadrant)

4. Liver function tests
Tests that measure Biosynthetic function of liver
Tests that measure Biosynthetic function of liver

5. Liver function tests
•The liver
–transaminases aspartate transaminase
–(AST or SGOT) and alanine transaminase
–(ALT or SGPT) are useful biomarkers of
–liver injury in a patient with some degree
–of intact liver function.[2][3][4] Most liver
–diseases cause only mild symptoms

6. Liver function tests
•initially, but these diseases must be
•detected early. Hepatic (liver)
•involvement in some diseases can be of
•crucial importance. This testing is
•performed on a patient's blood sample.
•Some tests are associated with
•functionality

7. Major Metabolic Functions of the Liver
•Synthetic Function
–Plasma proteins (albumin, globulins), cholesterol, triglycerides and
lipoproteins
•Detoxification and excretion
–Ammonia to urea (urea cycle), bilirubin, cholesterol, drug metabolites
•Storage Function
–Vitamins A, D, E, K and B
12
•Production of bile salts
–Helps in digestion

8. Some example of liver dysfunction
•Hepatocellular disease
•Cholestasis (obstruction of bile flow)
•Cirrhosis
•Hepatitis
•Jaundice
•Liver cancer
•Steatosis (fatty liver)
•Genetic Disorders
–Hemochromatosis (iron storage)

9. Liver Function Tests (LFTs)
•Noninvasive methods for screening of liver dysfunction
•Help in identifying general types of disorder
•Assess severity and allow prediction of outcome
•Disease and treatment follow up

10. Liver Function Tests (LFTs)
Broadly classified as:
1.Tests to detect hepatic injury:
•Mild or severe; acute or chronic
•Nature of liver injury (hepatocellular or cholestasis)
2.Tests to assess hepatic function

11. Classification of LFTs
Group I: Markers of liver dysfunction
▫Serum bilirubin: total and conjugated
▫Urine: bile salts and urobilinogen
▫Total protein, serum albumin and albumin/globulin ratio
▫Prothrombin Time

12. Classification of LFTs
Group II: Markers of hepatocellular injury
▫Alanine aminotransferase (ALT)
▫Aspartate aminotransferase (AST)

13. Classification of LFTs
Group III: Markers of cholestasis
▫Alkaline phosphatase (ALP)
▫g-glutamyltransferase (GGT)

14. What’s the diagnosis?
•Pt presents with insidious onset of fatigue, anorexia, nausea,
RUQ tenderness.He’s also noticed that his urine has been
darker for the past couple of daysand that his eyes have a
yellow hue.

15. Acute hepatitis
•AST
–Elevated
•ALT
–Elevated
•AlkPhos
–Normal 
Elevated
•T bili
–Normal 
Elevated
http://www.atsu.edu/faculty/chamberlain/Website/lectures/lecture/hepatit2.htm

16. •Fatty liver diseases
–Alcoholic liver disease
–NASH/NAFLD
•Viral hepatitis: HepB, C, D
•Autoimmune
–Autoimunehepatitis
–Primary biliary cirrhosis
–Primary sclerosingcholangitis
•Cardiovascular
–Budd-Chiarisyndrome
–Chronic right heart failure
cirrhosis Etiology
•Chronic biliary disease
–Recurrent bacterial cholangitis
–Bile duct stenosis
•Storage diseases
–Hemochromatosis
–Wilson disease
–α-1-antitrypsin deficiency
•Meds: APAP toxicity, MTX
•Cryptogenic 10-15%

17. •Fatty liver diseases
–Alcoholic liver disease
–NASH/NAFLD
•Viral hepatitis: HepB, C, D
•Autoimmune
–Autoimunehepatitis
–Primary biliary cirrhosis
–Primary sclerosingcholangitis
•Cardiovascular
–Budd-Chiarisyndrome
–Chronic right heart failure
cirrhosis Etiology
•Chronic biliary disease
–Recurrent bacterial cholangitis
–Bile duct stenosis
•Storage diseases
–Hemochromatosis
–Wilson disease
–α-1-antitrypsin deficiency
•Meds: APAP toxicity, MTX
•Cryptogenic 10-15%

18. Diagnostic imaging
•Ultrasound
–Surface nodularity: 88% sensitive, 82-95% specific
(1)
•CT insensitive in early cirrhosis
•MRI also insensitive in early cirrhosis, but
significant role in assessing small hepatocellular
carcinoma (HCC)—develops in 10-25%
•Liver biopsy = gold standard for diagnosis

19. Treatment
•Ascites
–Furosemide + Spironolactone with goal negative ~1L/day (~80% effective)
•Lasix: Aldactoneratio of 2:5 helps maintain K+ (thus Lasix 40mg qday, Aldactone100mg qdayinitially)
–Low-sodium diet (1-2 g/day)
•Refractory Ascites= no response on max doses of Lasix (160mg) & Aldactone
(400mg)
–LVP4-6L (does not improve mortality)
•Albumin replacement controversial. AASLD 2009 guidelines recommend if >5L removed, provide 6-8
g/L of albumin 25% (IIA, Grade C)
•If >5L removed, can have post-paracentesiscirculatory dysfxnvia RAAS activation
–TIPS (↓ ascites in 75%, improves mortality but ↑ HE, 40% need revision for stent
stenosis)

20. DDX for Acute hepatitis
•Shock liver: AST & ALT >50x ULN
•Drugs(e.g. Tylenol overdose, Isoniazid, Fenofibrate)
•Toxins(e.g. Alcohol, Muschrooms)
•Viral(e.gHepA, HepB, HSV, VZV, CMV, EBV): AST & ALT >25x ULN
•Wilson’s
•Vascular—Budd-Chiari
•AIH
•NASH: AST & ALT <4x ULN
•HELLP syndrome

21. Treatment
•Tylenol toxicity—N-acetylcysteine
•AIH–Prednisone60mg daily (taper)-azathioprine or 6-
mercaptopurine
•Budd-Chiari—TIPS
•Wilson’s dz—Plasma exchange to remove copper liver
transplant
•HepB—Antiviral therapy

22. Common serum liver chemistry tests

23. Liver function tests
•(e.g., albumin), some with
•cellular integrity (e.g., transaminase), and
•some with conditions linked to the biliary
•tract (gamma-glutamyl transferase and
•alkaline phosphatase).

24. •Several
•biochemical tests are useful in the
•evaluation and management of patients
•with hepatic dysfunction. These tests
•can be used to detect the presence of
•liver disease, distinguish among different
•types of liver disorders, gauge the extent
•of known liver damage, and follow the
•response to treatment.
Liver function tests

25. •Some or all of
•these measurements are also carried out
•(usually about twice a year for routine
•cases) on those individuals taking
•certain medications, such as
•anticonvulsants, to ensure the
•medications are not damaging the
•person's liver.
Liver function tests

26. •Although example reference ranges are
•given, these will vary depending on age,
•gender and his/her health, ethnicity,
•method of analysis, and units of
•measurement. Individual results should
•always be interpreted using the reference
•range provided by the laboratory that
•performed the test.
Liver function tests-Standard liver panel

27. Total bilirubin
•Reference range in adults
•Parameters/units Total bilirubin Unconjugated bilirubin
Conjugated bilirubin
•mg/dL 0.1–1.0[5] 0.2-0.7[5] 0.1–0.4[5]
•μmol/l 2.0 to 21[6] < 12[6] < 8[6]
•Measurement of total bilirubin includes
•both unconjugated (indirect) and

28. •conjugated (direct) bilirubin.
•Unconjugated bilirubin is a breakdown
•product of heme (a part of hemoglobin in
•red blood cells). The liver is responsible
•for clearing the blood of unconjugated
•bilirubin, by 'conjugating' it (modified to
•make it water-soluble) through an
•enzyme named UDP-glucuronyltransferase.
Total bilirubin

29. •When the total bilirubin level
•exceeds 17 μmol/l, it indicates liver
•disease. When total bilirubin level
•exceeds 40 μmol/l, bilirubin deposition at
•the sclera, skin, and mucous membranes
•will give these areas yellow colour, thus it
•is called jaundice

30. •The increase in predominantly
•unconjugated bilirubin is due to
•overproducion, reduced hepatic uptake of
•the unconjugated bilirubin and reduced
•conjugation of bilirubin. Overproduction
•can be due to reabsorption of
•haematomaand ineffective
•erythropoiesis that increased red blood
•cell destruction. Gilbert's syndrome and
•Crigler–Najjarsyndrome have defects in
•UDP glucuronyltransferasedefect,
•affecting bilirubin conjugation

31. •The degree of rise in conjugated bilirubin
•is directly proportional to the degree of
•hepatocyte injury. Viral hepatitis can also
•cause the rise in conjugated bilirubin.

32. •In parenchymal liver disease and
•incomplete extrahepaticobstruction, the rise in conjugated
bilirubin is less than the complete common bile duct
•obstruction due to malignant causes. In
•Dubin–Johnson syndrome, a mutation in
•multiple drug-resistance protein 2
•(MRP2) causes a rise in conjugated
•bilirubin

33. •In acute appendicitis, total bilirubin can
•rise from 20.52 μmol/l to 143 μmol/l. In
•pregnant women, the total bilirubin level
•is low in all three trimesters.[6]
•The measurement of bilirubin levels in
•the newborns is done through the use of
•bilimeter or transcutanoeus

34. •bilirubinometer instead of performing
•LFTs. When the total serum bilirubin
•increases over 95th percentile for age
•during the first week of life for high risk
•babies, it is known as hyperbilirubinemia
•of the newborn (neonatal jaundice) and
•requires light therapy to reduce the
•amount of bilirubin in the blood.

35. •Pathological jaundice in newbornsshouldbe suspected when
the serum bilirubin level rises by more than 5 mg/dL
•per day, serum bilirubin more than the
•physiological range, clinical jaundice
•more than 2 weeks, and conjugated
•bilirubin (dark urine staining clothes).
•Haemolyticjaundice is the commonest
•cause of pathological jaundice.

36. •Those
•babies with Rh hemolytic disease, ABO
•incompatibility with the mother, Glucose-
•6-phosphate dehydrogenase (G-6-PD)
•deficiency and minor blood group
•incompatibility are at increased risk of
•getting haemolytic jaundice

37. Alanine transaminase (ALT)
•Apart from being found in high concentrations in liver, ALT is
found in kidneys, heart, and muscles. It catalysesthe
transamination reaction, and only exists in cytoplasmic form.
Any kind of liver injury can cause the rise in ALT. A rise up to
300 IU/L is not specific to liver,
•but can be due to the damage of other
•organs such as kidneys or muscles.
•When ALT rises to more than 500 IU/L,
•causes are usually from the liver

38. Aspartate aminotransferase (AST)
•Normal range: 8 –20 U/L
•A marker of hepatocellular damage
•High serum levels are observed in:
–Chronic hepatitis, cirrhosis and liver cancer

39. Alanine aminotransferase (ALT)
•More liver-specific than AST
•Normal range (U/L):
▫Male: 13-35
▫Female: 10-30
•High serum levels in acute hepatitis (300-1000U/L)
•Moderate elevation in alcoholic hepatitis (100-300U/L)
•Minor elevation in cirrhosis, hepatitis C and non-alcoholic
steatohepatitis (NASH) (50-100U/L)

40. Alanine aminotransferase (ALT)
•Appears in plasma many days before clinical signs appear
•A normal value does not always indicate absence of liver
damage
•Obese but otherwise normal individuals may have elevated ALT
levels

41. Alkaline phosphatase (ALP)
•A non-specific marker of liver disease
•Produced by bone osteoblasts (for bone calcification)
•Present on hepatocyte membrane
•Normal range: 40 –125 U/L
•Modearte elevation observed in:
–Infective hepatitis, alcoholic hepatitis and hepatocellular carcinoma

42. Alkaline phosphatase (ALP)
•High levels are observed in:
–Extrahepatic obstruction (obstructive jaundice) and intrahepatic
cholestasis
•Very high levels are observed in:
–Bone diseases

43. g-glutamyltransferase (GGT)
•Used for glutathione synthesis
•Normal range: 10 –30U/L
•Moderate elevation observed in:
–Infective hepatitis and prostate cancers
•GGT is increased in alcoholics despite normal liver function
tests
–Highly sensitive to detecting alcohol abuse

44. •It can be due to hepatitis, ischemic liver injury, and toxins that
causes liver damage.
•TheALT levels in Hepatitis C rises more than in Hepatitis A and
B. Persistent ALT elevation more than 6 months is known as
chronic hepatitis.
•Alcoholic liver disease, Non-alcoholic fatty liver disease
(NAFLD), fat accumulation in liver during childhood obesity,
steatohepatitis(inflammation of fatty liver disease) are
associated with rise in ALT
Alanine transaminase (ALT)

45. •Rise in ALT is
•also associated with reduced insulin
•response, reduced glucose tolerance, and
•increased free fatty acids and
•triglycerides. Bright liver syndrome
•(bright liver on ultrasound suggestive of
•fatty liver) with raised ALT is suggestive
•of metabolic syndrome
Alanine transaminase (ALT)

46. •In pregnancy, ALT levels would rise during second trimester. In
one of the studies, measured ALT levels in pregnancy-related
conditions such as
•hyperemesis gravidarum was 103.5 IU/L,
•pre-eclampsiawas 115, HELLP syndrome
•was 149. ALT levels would reduce by
•greater than 50% in three days after child
•delivery.
Alanine transaminase (ALT)

47. •ALT levels would reduce by
•greater than 50% in three days after child
•delivery. Another study also shows that
•caffeine consumption can reduce the risk
•of ALT elevation in those who consume
•alcohol, overweight people, impaired
•glucose metabolism, and viral
•hepatitis
Alanine transaminase (ALT)

48. Aspartate transaminase (AST)
•AST exists in two isoenzymesnamely mitochondrial form and cytoplasmic form.
•It is found in highest concentration in the heart, followed by liver, muscle, and
•kidney.
•The increase of mitochondrial AST in bloods is highly suggestive of tissue necrosis in
myocardial infarction
•and chronic liver disease. More than 80%
•of the liver AST activity are contributed
•by mitochondrial form of the isoenzymes,
•while the circulating AST in blood are
•contributed by cytoplasmic form of AST

49. •AST is especially markedly raised in
•those with liver cirrhosis.[6] AST can be
•released from a variety of other tissues
•and if the elevation is less than two times
•the normal AST then no further workup
•needs to be performed if a patient is
•proceeding to surgery.
Aspartate transaminase (AST)

50. •In certain pregnancy conditions such as
•hyperemesis gravidarum, AST can reach
•as high as 73 IU/L, 66 IU/L in preeclampsia,
•and 81 IU/L in HELLP
•syndrome
Aspartate transaminase (AST)

51. AST/ALT ratio
•The AST/ALT ratio increases in liver functional impairment. In
alcoholic liver disease, the mean ratio is 1.45, and mean ratio is
1.33 in post necrotic liver cirrhosis.
•Ratio is greater than 1.17 in
•viral cirrhosis, greater than 2.0 in
•alcoholic hepatitis, and 0.9 in nonalcoholic
•hepatitis. Ratio is greater 4.5 in
•Wilson disease or hyperthyroidism

52. Alkaline phosphatase (ALP)

53. Bilirubin
•A byproduct of red blood cell breakdown
•It is the yellowish pigment observed in jaundice
•High bilirubin levels are observed in:
–Gallstones, acute and chronic hepatitis

56. Serum bilirubin levels
•Normal
–0.2 –0.8 mg/dL
•Unconjugated (indirect):
–0.2 –0.7 mg/dL
•Conjugated (direct):
–0.1 –0.4 mg/dL
•Latent jaundice:
–Above 1 mg/dL
•Jaundice:
–Above 2 mg/dL

57. Bilirubin levels and jaundice
Class of Jaundice Causes
Pre-hepatic or hemolytic Abnormal red cells; antibodies; drugs and toxins;
thalessemia
Hemoglobinopathies, Gilbert’s, Crigler-Najjar
syndrome
Hepatic or Hepatocellular Viral hepatitis, toxic hepatitis, intrahepatic
cholestasis
Post-hepatic Extrahepatic cholestasis; gallstones; tumors of the
bile duct, carcinoma of pancreas

58. Urobilinogen (UBG) and bile salts
•Most UBG is metabolized in the large intestine but a fraction is
excreted in urine (less than 4 mg/day)
•Normally bile salts are NOT present in urine
•Obstruction in the biliary passages causes:
–Leakage of bile salts into circulation
–Excretion in urine

59. Serum Albumin
•The most abundant protein synthesized by the liver
•Normal serum levels: 3.5 –5 g/dL
•Synthesis depends on the extent of functioning liver cell mass
•Longer half-life: 20 days
•Its levels decrease in all chronic liver diseases

60. Serum Globulin
•Normal serum levels: 2.5 –3.5g/dL
•aand b-globulins mainly synthesized by the liver
•They constitute immunoglobulins (antibodies)
•High serum g-globulins are observed in chronic hepatitis and
cirrhosis:
–IgG in autoimmune hepatitis
–IgA in alcoholic liver disease

61. Albumin to globulin (A/G) ratio
•Normal A/G ratio: 1.2/1 –1.5/1
•Globulin levels increase in hypoalbuminemia as a
compensation

62. Prothrombin Time (PT)
•Prothrombin: synthesized by the liver, a marker of liver
function
•Half-life: 6 hrs. (indicates the present function of the liver)
•PT is prolonged only when liver loses more than 80% of its
reserve capacity
•Vitamin K deficiency also causes prolonged PT
•Intake of vitamin K does not affect PT in liver disease

63. Take Home Messages
•LFTs help detect liver injury and function.
•LFTs do have some limitations.

64. References
•Lippincott’s Illustrated Reviews Biochemistry: 6
th
edition, Unit IV, Chapter 21, Pages
282 -285.
•Lecture notes: Clinical Biochemistry: 9
th
edition, Chapter 13, Pages 174 -187.
•Clinical Chemistry -Techniques, Principales and Correlations: 6
th
edition, Chapter 24,
Pages 520 -521.